PROJECT SUMMARY: Recent advances in venomics, the genomics and proteomics of venoms, are providing exciting opportunities to expand our understanding of the biology of venoms and venom-derived toxins. Numerous therapeutic circumstances are inefficiently attended by the existing drug resource and signify important unmet needs for enormous populations of patients. Natural products have been a main foundation of drug design and snake as well as other animal venoms have a vast unexploited potential. The National Natural Toxins Research Center is in need of equipment crucial for analyzing the effects of toxins on various cell lines, purifying venom toxins, and designing, based on cDNA data, novel molecules with innovative modes of action. The equipment being requested, BD Accuri? C6 Plus flowcytometer, a Waters? Binary High Preformance Liquid Chromatography System, and a Tribute UV-IR Benchtop Peptide Synthesizer, in the proposal are ideally suited to support critical research by, detecting targets and determining their effects on various cell lines, purifying venom molecules, and designing novel molecules that can be used in therapeutics. The additional specific aims for the supplemental grant will be to: 1) develop new toxins that will lead to the effective design of neutralizing molecules as well as understanding toxin-cellular target interactions; 2) provide a research environment in which faculty and students will be highly trained on state-of-the-art instrumentation; and 3) provide a research environment that will encourage more students to pursue careers in biomedical research. Access to these instruments will enable researchers to make important advances in the search for venom- derived therapeutics and for the development of novel strategies for venom antidotes. RELEVANCE: Significant advancements for various disease treatments is accredited to venom derived molecules, such as ACE inhibitors, Integrilin, and Prialt. These novel molecules are currently used in the treatment of major medical diseases like strokes, heart attacks, and chronic pain. In addition to providing support for the NNTRC?s venom research program, the instruments will provide undergraduate and graduate trainees with the understanding and opportunity for hands-on training in protein sequencing and its applications to biomedical research.